-
Journal of Food Protection Feb 2021Shewanella baltica, one of the dominant spoilers of seafoods, can synthesize putrescine from ornithine under acidic conditions, which could result in food spoilage and...
ABSTRACT
Shewanella baltica, one of the dominant spoilers of seafoods, can synthesize putrescine from ornithine under acidic conditions, which could result in food spoilage and health problems. We identified three regulatory enzymes (SpeC, SpeF, and PotE) in the ornithine decarboxylation (ODC) pathway of S. baltica by searching the NCBI database and exploring their functional roles through gene knock-out technology. The ornithine decarboxylase SpeC is an auxiliary adjustor of the ODC system, whereas the ornithine-putrescine transporter SpeE and ornithine decarboxylase SpeF participate in the production of extracellular putrescine. Exogenous addition of ornithine and putrescine promotes the extracellular secretion of putrescine by upregulating the expression of speF and potE. The putrescine biosynthesis and alkalization of cytoplasm is enhanced at weak acidic pH compared with neutral pH, especially at pH 6.0. The maximum upregulation of ODC genes and the optimum decarboxylation activity of SpeF are achieved in a weak acidic environment (pH 6.0), suggesting that the ODC pathway plays an important role in putrescine production and the cytoplasmic acid counteraction of S. baltica. This study contributes to a wider understanding of spoilage mechanisms in food systems and provides theoretical support for developing novel seafood preservation methods.
Topics: Decarboxylation; Ornithine; Putrescine; Shewanella
PubMed: 33003195
DOI: 10.4315/JFP-20-227 -
OncoTargets and Therapy 2021Polyamines are multivalent organic cations essential for many cellular functions, including cell growth, differentiation, and proliferation. However, elevated polyamine... (Review)
Review
Polyamines are multivalent organic cations essential for many cellular functions, including cell growth, differentiation, and proliferation. However, elevated polyamine levels are associated with a slew of pathological conditions, including multiple cancers. Intracellular polyamine levels are primarily controlled by the autoregulatory circuit comprising two different protein types, Antizymes (OAZ) and Antizyme Inhibitors (AZIN), which regulate the activity of the polyamine biosynthetic enzyme ornithine decarboxylase (ODC). While OAZ functions to decrease the intracellular polyamine levels by inhibiting ODC activity and exerting a negative control of polyamine uptake, AZIN operates to increase intracellular polyamine levels by binding and sequestering OAZ to relieve ODC inhibition and to increase polyamine uptake. Interestingly, OAZ and AZIN exhibit autoregulatory functions on polyamine independent pathways as well. A growing body of evidence demonstrates the dysregulation of AZIN expression in multiple cancers. Additionally, RNA editing of the transcript results in a "gain-of-function" phenotype, which is shown to drive aggressive tumor types. This review will discuss the recent advances in AZIN's role in cancers via aberrant polyamine upregulation and its polyamine-independent protein regulation. This report will also highlight AZIN interaction with proteins outside the polyamine biosynthetic pathway and its potential implication to cancer pathogenesis. Finally, this review will reveal the protein interaction network of AZIN isoforms by analyzing three different interactome databases.
PubMed: 33531815
DOI: 10.2147/OTT.S281157 -
Frontiers in Plant Science 2019Ornithine decarboxylase (ODC) catalyzes ornithine decarboxylation to yield putrescine, a key precursor of polyamines, and tropane alkaloids (TAs). Here, to investigate...
Ornithine decarboxylase (ODC) catalyzes ornithine decarboxylation to yield putrescine, a key precursor of polyamines, and tropane alkaloids (TAs). Here, to investigate in depth the role of ODC in polyamine/TA biosynthesis and to provide a candidate gene for engineering polyamine/TA production, the ODC gene () was characterized from , a TA-producing plant. Our phylogenetic analysis revealed that HnODC was clustered with ODC enzymes of plants. Experimental work showed highly expressed in roots and induced by methyl jasmonate (MeJA). In the MeJA treatment, the production of both putrescine and -methylputrescine were markedly promoted in roots, while contents of putrescine, spermidine, and spermine were all significantly increased in leaves. By contrast, MeJA did not significantly change the production of either hyoscyamine or scopolamine in plants. Building on these results, the 50-kDa His-tagged HnODC proteins were purified for enzymatic assays. When ornithine was fed to HnODC, the putrescine product was detected by HPLC, indicating HnODC catalyzed ornithine to form putrescine. Finally, we also investigated the enzymatic kinetics of HnODC. Its , , and values for ornithine were respectively 2.62 ± 0.11 mM, 1.87 ± 0.023 nmol min μg and 1.57 ± 0.015 s, at pH 8.0 and at 30°C. The HnODC enzyme displays a much higher catalytic efficiency than most reported plant ODCs, suggesting it may be an ideal candidate gene for engineering polyamine/TA biosynthesis.
PubMed: 30873201
DOI: 10.3389/fpls.2019.00229 -
Molecules (Basel, Switzerland) Jul 2019l-Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis in humans and fungi. Elevated levels of polyamine by over-induction of ODC activity...
l-Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis in humans and fungi. Elevated levels of polyamine by over-induction of ODC activity in response to tumor-promoting factors has been frequently reported. Since ODC from fungi and human have the same molecular properties and regulatory mechanisms, thus, fungal ODC has been used as model enzyme in the preliminary studies. Thus, the aim of this work was to purify ODC from fungi, and assess its kinetics of inhibition towards various compounds. Forty fungal isolates were screened for ODC production, twenty fungal isolates have the higher potency to grow on L-ornithine as sole nitrogen source. was the most potent ODC producer (2.1 µmol/mg/min), followed by and . These isolates were molecularly identified based on their ITS sequences, which have been deposited in the NCBI database under accession numbers MH156195, MH155304 and MH152411, respectively. ODC was purified and characterized from using SDS-PAGE, showing a whole molecule mass of ~110 kDa and a 50 kDa subunit structure revealing its homodimeric identity. The enzyme had a maximum activity at 37 °C, pH 7.4-7.8 and thermal stability for 20 h at 37 °C, and 90 days storage stability at 4 °C. ODC had a maximum affinity () for l-ornithine, l-lysine and l-arginine (0.95, 1.34 and 1.4 mM) and catalytic efficiency (/) (4.6, 2.83, 2.46 × 10 mM·s). The enzyme activity was strongly inhibited by DFMO (0.02 µg/mL), curcumin (IC 0.04 µg/mL), propargylglycine (20.9 µg/mL) and hydroxylamine (32.9 µg/mL). These results emphasize the strong inhibitory effect of curcumin on ODC activity and subsequent polyamine synthesis. Further molecular dynamic studies to elucidate the mechanistics of ODC inhibition by curcumin are ongoing.
Topics: Aspergillus; Enzyme Activation; Kinetics; Molecular Weight; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Structure-Activity Relationship; Substrate Specificity
PubMed: 31362455
DOI: 10.3390/molecules24152756 -
Cell Communication and Signaling : CCS Jan 2024Metabolism of polyamines is of critical importance to physiological processes. Ornithine decarboxylase (ODC) antizyme inhibitors (AZINs) are capable of interacting with... (Review)
Review
Metabolism of polyamines is of critical importance to physiological processes. Ornithine decarboxylase (ODC) antizyme inhibitors (AZINs) are capable of interacting with antizymes (AZs), thereby releasing ODC from ODC-AZs complex, and promote polyamine biosynthesis. AZINs regulate reproduction, embryonic development, fibrogenesis and tumorigenesis through polyamine and other signaling pathways. Dysregulation of AZINs has involved in multiple human diseases, especially malignant tumors. Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans. Additionally, the high frequencies of RNA-edited AZIN1 in human cancers correlates with increase of cancer cell proliferation, enhancement of cancer cell stemness, and promotion of tumor angiogenesis. In this review, we summarize the current knowledge on the various contribution of AZINs related with potential cancer promotion, cancer stemness, microenvironment and RNA modification, especially underlying molecular mechanisms, and furthermore explored its promising implication for cancer diagnosis and treatment.
Topics: Humans; Ornithine Decarboxylase; Translational Research, Biomedical; Polyamines; Cell Transformation, Neoplastic; RNA; Tumor Microenvironment
PubMed: 38169396
DOI: 10.1186/s12964-023-01445-1 -
The Journal of Biological Chemistry 2021The siderophore rhizoferrin (N,N-dicitrylputrescine) is produced in fungi and bacteria to scavenge iron. Putrescine-producing bacterium Ralstonia pickettii synthesizes...
The siderophore rhizoferrin (N,N-dicitrylputrescine) is produced in fungi and bacteria to scavenge iron. Putrescine-producing bacterium Ralstonia pickettii synthesizes rhizoferrin and encodes a single nonribosomal peptide synthetase-independent siderophore (NIS) synthetase. From biosynthetic logic, we hypothesized that this single enzyme is sufficient for rhizoferrin biosynthesis. We confirmed this by expression of R. pickettii NIS synthetase in Escherichia coli, resulting in rhizoferrin production. This was further confirmed in vitro using the recombinant NIS synthetase, synthesizing rhizoferrin from putrescine and citrate. Heterologous expression of homologous lbtA from Legionella pneumophila, required for rhizoferrin biosynthesis in that species, produced siderophore activity in E. coli. Rhizoferrin is also synthesized by Francisella tularensis and Francisella novicida, but unlike R. pickettii or L. pneumophila, Francisella species lack putrescine biosynthetic pathways because of genomic decay. Francisella encodes a NIS synthetase FslA/FigA and an ornithine decarboxylase homolog FslC/FigC, required for rhizoferrin biosynthesis. Ornithine decarboxylase produces putrescine from ornithine, but we show here in vitro that FigA synthesizes N-citrylornithine, and FigC is an N-citrylornithine decarboxylase that together synthesize rhizoferrin without using putrescine. We co-expressed F. novicida figA and figC in E. coli and produced rhizoferrin. A 2.1 Å X-ray crystal structure of the FigC N-citrylornithine decarboxylase reveals how the larger substrate is accommodated and how active site residues have changed to recognize N-citrylornithine. FigC belongs to a new subfamily of alanine racemase-fold PLP-dependent decarboxylases that are not involved in polyamine biosynthesis. These data reveal a natural product biosynthetic workaround that evolved to bypass a missing precursor and re-establish it in the final structure.
Topics: Bacterial Proteins; Citrates; Ferric Compounds; Francisella; Iron; Legionella pneumophila; Peptide Synthases; Putrescine; Ralstonia pickettii; Siderophores
PubMed: 33277357
DOI: 10.1074/jbc.RA120.016738 -
Food Science & Nutrition Sep 2022strains have been reported to be useful in biotechnological and probiotic determinations, and some of them are considered opportunistic pathogens. Given the widespread...
strains have been reported to be useful in biotechnological and probiotic determinations, and some of them are considered opportunistic pathogens. Given the widespread interest about antimicrobial susceptibilities, transmission of resistances, and virulence factors, there is little research available on such topics for . The aim of this study was to assess the safety aspects and antimicrobial potential of 54 spp. strains from different environmental sources. Antibiotic susceptibility, hemolytic activity, horizontal transfer, and antibacterial activity were studied, as well as the detection of biogenic amine BA production on decarboxylase medium and PCR was performed. All the strains were nonhemolytic and sensitive to chloramphenicol and ampicillin. Several strains were classified as resistant to fusidic acid, and very low resistance rates were detected to ciprofloxacin, tetracycline, streptomycin, lincomycin, erythromycin, and rifampicin, although all strains had intrinsic resistance to vancomycin, nalidixic acid, kanamycin, and teicoplanin. Two BA-producing strains (. FAS30 and FAS29) exhibited tyrosine decarboxylase activity, and just one . FS077 produced both tyramine and histamine, and their genetic determinants were identified. Ornithine decarboxylase/ gene was found in 16 of the strains, although 3 of them synthesize putrescine. Interestingly, eight strains with good properties displayed antibacterial activity. Conjugation frequencies of erythromycin from to spp. varied in the average of 3 × 10 transconjugants/recipient. However, no tetracycline-resistant transconjugant was obtained with JH2-2 as recipient. The obtained results support the safe status of strains, derived from environmental sources, when used as probiotics in animal feed.
PubMed: 36171785
DOI: 10.1002/fsn3.2885 -
BMC Gastroenterology Jun 2023Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium...
BACKGROUND
Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease.
METHODS
The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB.
RESULTS
Triptolide didn't have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon.
CONCLUSION
The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.
Topics: Animals; Rats; Irritable Bowel Syndrome; Diterpenes; Phenanthrenes
PubMed: 37308808
DOI: 10.1186/s12876-023-02847-8 -
CNS Oncology Apr 2018This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that... (Review)
Review
This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that irreversibly inhibits the enzyme ornithine decarboxylase. It covers the use of eflornithine, alone or in combination, to treat high-grade gliomas. In addition, we provide an update on overall survival from The University of Texas MD Anderson Cancer Center Community Clinical Oncology Program and Clinical Trials Data Office that demonstrates a meaningful benefit in overall survival for eflornithine as a single agent and in combination with nitrosourea-based therapies for anaplastic gliomas. We also provide a framework for understanding the basis and study design of the ongoing pivotal, registrational Phase III multicenter trial for recurrent/progressive anaplastic astrocytoma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Eflornithine; Glioma; Humans
PubMed: 29378419
DOI: 10.2217/cns-2017-0031 -
Journal of Assisted Reproduction and... Mar 2019The aging-related decline in fertility is an increasingly pressing medical and economic issue in modern society where women are delaying family building. Increasingly... (Review)
Review
The aging-related decline in fertility is an increasingly pressing medical and economic issue in modern society where women are delaying family building. Increasingly sophisticated, costly, and often increasingly invasive, assisted reproductive clinical protocols and laboratory technologies (ART) have helped many older women achieve their reproductive goals. Current ART procedures have not been able to address the fundamental problem of oocyte aging, the increased rate of egg aneuploidy, and the decline of developmental potential of the eggs. Oocyte maturation, which is triggered by luteinizing hormone (LH) in vivo or by injection of human chorionic gonadotropin (hCG) in an in vitro fertilization (IVF) clinic, is the critical stage at which the majority of egg aneuploidies arise and when much of an egg's developmental potential is established. Our proposed strategy focuses on improving egg quality in older women by restoring a robust oocyte maturation process. We have identified putrescine deficiency as one of the causes of poor egg quality in an aged mouse model. Putrescine is a biogenic polyamine naturally produced in peri-ovulatory ovaries. Peri-ovulatory putrescine supplementation has reduced egg aneuploidy, improved embryo quality, and reduced miscarriage rates in aged mice. In this paper, we review the literature on putrescine, its occurrence and physiology in living organisms, and its unique role in oocyte maturation. Preliminary human data demonstrates that there is a maternal aging-related deficiency in ovarian ornithine decarboxylase (ODC), the enzyme responsible for putrescine production. We argue that peri-ovulatory putrescine supplementation holds great promise as a natural and effective therapy for infertility in women of advanced maternal age, applicable in natural conception and in combination with current ART therapies.
Topics: Abortion, Spontaneous; Adult; Aging; Female; Fertilization in Vitro; Humans; Infertility, Female; Middle Aged; Oocytes; Oogenesis; Ornithine Decarboxylase; Ovary; Pregnancy; Putrescine; Reproduction
PubMed: 30467617
DOI: 10.1007/s10815-018-1327-x